Postoperative delirium is one of the most common complications following cardiac surgery. This major health problem costs the US health system billions of dollars annually. Apart from its psychological and physical toll on patients and caregivers, delirium interferes with rehabilitation following surgery. Diagnosis of delirium is urgent as it places compromised individuals at risk for self-injury and falls. It has an establishe association with subsequent mortality and long-term cognitive impairment. Despite a postoperative incidence of up to 50% for cardiac surgery, known risk factors do not reliably predict which individuals will experience delirium. While a single underlying pathophysiologic pathway is unlikely, cases share an exposure to perioperative precipitating factors and potentially vulnerability against these insults. Biomarkers are urgently needed to quantify this susceptibility and track the development of postoperative delirium. Their identification would serve as a major step toward treatment and prevention. Accumulated neuroimaging evidence suggest that the strength of correlated neural activity among spatially distributed brain regions, known as the default mode network (DMN), may be informative. This proposal, The Default Mode Network during the Pathogenesis of Postoperative Delirium, will longitudinally probe the relationship between the DMN and delirium in the perioperative period. It will establish that the development of delirium and severity of symptoms are mirrored by fluctuations in correlated activity within the DMN. We expect this investigation to provide a lasting impact on perioperative medicine. Preoperative stratification for delirium vulnerability could inform patients and their families regarding the likelihood of potential cognitive trajectories after elective procedures. Fo health care practitioners, identification of vulnerable patients before surgery could focus on diagnostics and optimization. Postoperatively, an imaging biomarker for tracking the development of delirium could assess the efficacy of preventative measures and treatment. Overall, this proposal is designed as an innovative approach to bring functional brain imaging technology to bear on reducing the incidence and severity of this (rightly) feared complication of surgical interventions.